A5038446513- Trypanosoma species research and implications
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Metal complexes synthesis and properties
- Research on Leishmaniasis Studies
- X-ray Diffraction in Crystallography
- HIV/AIDS drug development and treatment
- Chemical Thermodynamics and Molecular Structure
- SARS-CoV-2 and COVID-19 Research
- Crystal structures of chemical compounds
- Glycosylation and Glycoproteins Research
- Crystallization and Solubility Studies
- Magnetism in coordination complexes
- Synthesis and Biological Evaluation
- Synthesis and biological activity
- Lanthanide and Transition Metal Complexes
- Carbohydrate Chemistry and Synthesis
- Malaria Research and Control
- Enzyme Production and Characterization
- Biotechnology and Related Fields
- Venomous Animal Envenomation and Studies
- Viral Infections and Vectors
- Protein Structure and Dynamics
Universidade de São Paulo
2016-2025
Universidade Federal de São Carlos
2013-2024
Santa Casa de Misericórdia de São Carlos
2018
Birkbeck, University of London
1988-2011
Instituto Internacional de Ecologia (Brazil)
2011
Universidade Federal de Pernambuco
2010
Universidade Federal da Bahia
2010
International Union of Pure and Applied Chemistry
2010
Rede de Química e Tecnologia
2010
Instituto de Biología Molecular y Celular de Rosario
2007
SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (Mpro) an attractive target for antivirals. clinically approved drug nirmatrelvir and clinical candidate ensitrelvir have so far showed great potential treatment infection. However, broad use antivirals often associated with resistance generation. Herein, we enzymatically characterized 14 naturally occurring Mpro polymorphisms that are close to binding site these Nirmatrelvir retained its potency against most tested,...
Abstract The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development novel efficacious safe antiviral drugs. Due to its central role in RNA viral replication, non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is prime target for drug discovery. Here we describe crystal structure recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as platform...
Bothropstoxin I (BthTX-I) from the venom of Bothrops jararacussuis a myotoxic phospholipase A2 (PLA2) homologue which, although catalytically inactive due to an Asp49→Lys substitution, disrupts integrity lipid membranes by Ca2+-independent mechanism. The crystal structures two dimeric forms BthTX-I which diffract X-rays resolutions 3.1 and 2.1 Å have been determined. monomers in both are related almost perfect twofold axis rotation dimer interfaces defined contacts between N-terminal...
Background The yellow fever mosquito, Aedes aegypti, is the primary vector for viruses that cause fever, mostly in tropical regions of Africa and parts South America, human dengue, which infects 100 million people yearly tropics subtropics. A better understanding structural biology olfactory proteins may pave way development environmentally-friendly mosquito attractants repellents, ultimately contribute to reduction biting disease transmission. Methodology Previously, we isolated cloned a...
The development of cruzain inhibitors has been driven by the urgent need to develop novel and more effective drugs for treatment Chagas' disease. Herein, we report lead optimization a class noncovalent inhibitors, starting from an inhibitor previously cocrystallized with enzyme (K(i) = 0.8 μM). With goal achieving better understanding structure-activity relationships, have synthesized evaluated series over 40 analogues, leading very promising competitive (8r, IC50 200 nM, K(i) 82 nM)....
With the rapidly evolving SARS-CoV-2 variants of concern, there is an urgent need for discovery further treatments coronavirus disease (COVID-19). Drug repurposing one most rapid strategies addressing this need, and numerous compounds have already been selected in vitro testing by several groups. These led to a growing database molecules with activity against virus. Machine learning models can assist drug through prediction best based on previously published data. Herein, we implemented...
A total of 39 endophytic fungi have been isolated from Viguiera arenaria and Tithonia diversifolia, both collected in São Paulo State, Brazil. The isolates were identified based on their ribosomal DNA sequences. ethyl acetate (EtOAc) extracts all evaluated for antimicrobial, antiparasitic antitumoral activity. Antimicrobial screening was conducted using an agar diffusion assay against three pathogenic microorganisms: Staphylococcus aureus, Escherichia coli Candida albicans. Antiparasitic...
NEW DRUGS.Neglected diseases are a major global cause of illness, long-term disability and death.Chagas' disease is parasitic infection widely distributed throughout Latin America, with devastating consequences in terms human morbidity mortality.The existing drug therapy suffers from combination drawbacks including poor efficacy, resistance serious side effects.In 2009, we celebrate the 100 th anniversary discovery Chagas' disease, facing challenges developing new, safe effective drugs for...
The discovery of the pharmacological functions nitric oxide has led to development NO donor compounds as therapeutic agents. A new generation ruthenium donors, cis-[Ru(NO)(bpy)(2)L]X(n), been developed, and our aim was show that these complexes are able lyse Trypanosoma cruzi in vitro vivo.NO donors were incubated with T. their anti-T. activities evaluated percentage lysed parasites compared negative control. In vivo, trypanocidal activity by observing levels parasitaemia, survival rate...
Based on its essential role in the life cycle of Trypanosoma cruzi, glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been considered a promising target for development novel chemotherapeutic agents treatment Chagas' disease. In course our research program to discover inhibitors this trypanosomatid enzyme, we have explored combination structure and ligand-based virtual screening techniques as complementary approach biochemical natural products using standard assay. Seven...
There are currently relatively few small-molecule antiviral drugs that either approved or emergency-approved for use against severe acute respiratory coronavirus 2 (SARS-CoV-2). One of these is remdesivir, which was originally repurposed from its Ebola. We evaluated three molecules we had previously identified computationally with activity Ebola and Marburg pyronaridine, inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The vivo efficacy pyronaridine has now been assessed a K18-hACE...
The main protease from SARS-CoV-2 (Mpro) is responsible for cleavage of the viral polyprotein. Mpro self-processing called maturation, and it crucial enzyme dimerization activity. Here we use C145S to study structure dynamics N-terminal in solution. Native mass spectroscopy analysis shows that mixed oligomeric states are composed cleaved uncleaved particles, indicating processing not critical dimerization. A 3.5 Å cryo-EM provides details outside constrains crystal environment. We show...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, highly conserved and plays a critical role in ability virus to evade immune system. NendoU promising target for development new antiviral drugs. However, complexity enzyme's structure kinetics, along with broad range recognition sequences lack structural complexes, hampers inhibitors. Here, we performed enzymatic...
The structure of the enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) from glycosomes parasite Trypanosoma cruzi , causative agent Chagas' disease, is reported. final model at 2.8 Å includes bound cofactor NAD + and 90 water molecules per monomer resulted in an R factor 20.1%, free =22.3%, with good geometry indicators. has no ions active site resulting a large change side chain conformation Arg 249 which as consequence forms salt bridge to Asp 210 present structure. We propose that...